Objective The aim of this study was to assess the association between plasma leptin levels and serum C-peptide levels in type 2 diabetic patients. Methods Three hundred and sixty-nine type 2 diabetic patients (DM) (M: 183, F: 186) were recruited. Plasma leptin levels were measured. Fasting and postprandial 2-hour serum C-peptide levels were measured. Results The mean age of subjects was 60.7 ± 13.3 years. The mean DM duration, HbA1C, and body mass index (BMI) was 8.1 ± 7.9 years, 8.6 ± 2.3%, and 24.8 ± 4.1 kg/m², respectively. BMI, waist circumference, total cholesterol, triglyceride, serum fasting, postprandial C-peptide and ∇C-pepdie levels tended to be higher in patients with an increased plasma leptin level. Serum fasting C-peptide, postprandial C-peptide and ∇C-pepdie levels correlated positively with plasma leptin levels, respectively (r = 0.228, P < 0.001; r = 0.208, P < 0.001; r = 0.137, P = 0.009, respectively). In a multivariate analysis, plasma leptin levels were independently associated with fasting, postprandial, and ∇C-peptide levels, after adjustment for confounding factors including age, gender, BMI, HbA1C, diabetes duration, blood glucose, and total cholesterol. Conclusion This study showed that plasma leptin levels were positively associated with serum C-peptide levels regardless of anthropometric and metabolic parameters.